Introduction: Cannabis occupies the position of the most prevalent drug of abuse in Egypt. Chronic cannabis abuse may cause degenerative pathological changes in the brain, also the effect of cannabis on cognition, memory and learning is well known. The current work aimed to study the toxic effect of chronic repeated doses of cannabis on rat behavior, brain dopamine level and histopathological changes of the brain. Subjects and Methods: The study was conducted on 50 male albino rats weighing 180-200 gm. Rats were divided into 2 main groups: group 1 (control; each animal received 1ml/day 100% sunflower oil (used as a vehicle); group 2 (received cannabis daily for one month "40 mg cannabis/ 200 gm rat". At the end of the month this group was subdivided into 4 subgroups: subgroups 2a, 2b, 2c, and 2d and subjected to different periods of cannabis abstinence. The clinical manifestations due to the effect of long-term cannabis administration and withdrawal were recorded. After scarification, brain dopamine level was measured, and brain tissue was examined by light and electron microscope (EM). Results: Clinically; main manifestations of long-term cannabis administration found in subgroup 2a were CNS depression; while main manifestations in subgroup 2c were irritability and fighting aggression. Dopamine significantly increased in subgroup 2a compared to control group. Light and EM examination showed degenerative changes. Conclusion: Brain dopamine level was significantly high in subgroup 2a compared with control group. long-term cannabis administration causes degenerative pathological changes in the brain, which need long recovery periods.